title: Serum endogenous secretory RAGE level is an independent risk factor for the progression of carotid atherosclerosis in type 1 diabetes.
abstract: OBJECTIVE
  Advanced glycation end-products (AGEs) and the receptor for AGEs (RAGE) system plays an important role in the development of atherosclerosis. It has been recently reported that endogenous secretory RAGE (esRAGE) and total soluble RAGE (sRAGE) levels are associated with diabetic complications. The aim of the present study is to longitudinally evaluate the association between esRAGE and sRAGE levels and the progression of carotid intima-media thickness (IMT), a surrogate marker of atherosclerosis.
  
  
  RESULTS
  Japanese type 1 diabetic patients (n=47, aged 24.0+/-3.1 years) were enrolled into a 4-year follow-up study and annual measurements of serum esRAGE and sRAGE levels and IMTs were performed. At baseline, mean-IMT was inversely correlated with circulating esRAGE levels (r=-0.317, p=0.0292), whereas there was not statistical significance between mean-IMT and sRAGE levels. Mean-IMT significantly increased during the follow-up period (from 0.63+/-0.10 to 0.67+/-0.10mm, p=0.0022). Annual increase in mean-IMT (=(mean-IMT after 4 years-mean-IMT at baseline)/4) was positively correlated with the arithmetic average of systolic blood pressure (r=0.310, p=0.0332) and triglyceride (r=0.337, p=0.0201), and inversely correlated with circulating esRAGE levels (r=-0.360, p=0.0124) and sRAGE levels (r=-0.406, p=0.0042) during the follow-up period. Furthermore, stepwise multivariate regression analyses revealed that continuous low levels of circulating esRAGE and sRAGE were determinants of the progression of mean-IMT independently of conventional risk factors.
  
  
  CONCLUSIONS
  Circulating esRAGE level as well as sRAGE level was an independent risk factor for the progression of carotid IMT in type 1 diabetic subjects.
authors.affiliation: Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, Suita, Osaka, Japan. katakami@medone.med.osaka-u.ac.jp
authors.forename: Naoto
authors.initials: N
authors.lastname: Katakami
authors.forename: Munehide
authors.initials: M
authors.lastname: Matsuhisa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kaneto
authors.forename: Taka-aki
authors.initials: TA
authors.lastname: Matsuoka
authors.forename: Ken'ya
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Tetsuyuki
authors.initials: T
authors.lastname: Yasuda
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Umayahara
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kosugi
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Yamasaki
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002340:Carotid Artery Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology*; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging; D002343:Carotid Artery, Internal / Q000000981:diagnostic imaging; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D007564:Japan; D015999:Multivariate Analysis; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D017539:Tunica Intima / Q000000981:diagnostic imaging; D017540:Tunica Media / Q000000981:diagnostic imaging; D014463:Ultrasonography; D055815:Young Adult
chemical_list: D015415:Biomarkers; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic